Successful chemotherapy of experimental neuroendocrine lung tumors in hamsters with an antagonist of Ca2+/calmodulin.
The chemotherapeutic effect of B859-35, the (-)-enantiomer of dihydropyrine 3-methyl-5-3-(4,4-diphenyl-1-piperidinyl)-propyl-1,4-dihydro-2,6-dimethy l-4- (3-nitrophenyl)-pyridine-3,5-dicarboxylate-hydrochloride (niguldipine), was tested on tumors induced in Syrian golden hamsters by N-nitrosodiethylamine (DEN). Peripheral pulmonary adenomas/adenocarcinomas were induced in hamsters maintained under ambient air conditions by multiple s.c. injections of DEN for 20 weeks. We have reproducibly shown that within this time interval lung adenomas develop in a significant number of the animals. The carcinogen treatment was discontinued at this point and one group of these hamsters was given B859-35 intragastrically 5 days/week for 20 weeks while the second group of such tumor-bearing hamsters were kept for an identical time interval without further treatment. Neuroendocrine lung tumors were induced in hamsters maintained in an atmosphere of 60% O2 by multiple s.c. injections of DEN for 8 weeks. We have reproducibly shown that within this short time interval neuroendocrine lung tumors develop in a significant number of the animals. The carcinogen treatment was discontinued at this point and the animals were returned to ambient air conditions. One group of these tumor-bearing hamsters was then given B859-35 intragastrically 5 days/week for 20 weeks while a second group of these hamsters was kept untreated for an identical time interval. A control group was given s.c. injections of saline for 20 weeks under ambient air conditions. A dramatic and selective anticarcinogenic effect of B859-35 was observed on the neuroendocrine lung tumors and nasal cavity tumors induced by DEN/hyperoxia while tumors of larynx/trachea were not affected. B859-35 had no effect on peripheral adenomas/adenocarcinomas, nasal cavity tumors, papillary polyps of larynx/trachea, or liver tumors induced by DEN under ambient air conditions.
Schuller
H M
HM
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
Correa
E
E
Orloff
M
M
Reznik
G K
GK
D000818:Animals; D006224:Cricetinae; D004052:Diethylnitrosamine; D004095:Dihydropyridines / Q000627:therapeutic use*; D007822:Laryngeal Neoplasms / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D009669:Nose Neoplasms / Q000139:chemically induced; D014134:Tracheal Neoplasms / Q000139:chemically induced
D004095:Dihydropyridines; D004052:Diethylnitrosamine; C054074:niguldipine